Witte was first to develop methods to culture B lineage cells, co-discovered the tyrosine kinase (TyK) gene family, showed that a TyK is responsible for congenital human B cell immunodeficiencies and that the fusion of ABL, a TyK, to the BCR gene in the Philadelphia chromosome is critical for leukemogenesis.

Research Interests

My laboratory is concerned with the interrelated problems of cell growth regulation and differentiation and understanding the function of oncogenes found in human leukemias and epithelial cancers. This includes the Bcr-Abl tyrosine kinase important in human chronic myelogenous leukemia. We are also interested in understanding the regulation of lymphocyte growth in disease states and during immune responses. We discovered that the gene defect in the primary immunodeficiency X-linked agammaglobulinemia is a single gene called Bruton's tyrosine kinase and are now studying its mode of action. Recently, we identified a G protein-coupled receptor family which regulates inflammatory responses and autoimmunity and are studying its mechanisms of action. We are using PET and other imaging modalities to study lymphocyte movement during the immune response as regulated by these receptors. Prostate cancer is unique in its highly regularized pattern of metastasis to the bone marrow. One possible therapeutic target is PSCA (prostate homolog of hematopoietic stem cell antigen) expressed on a subset of prostate cells during active growth. We are using surface markers to fractionate normal murine prostate cell populations in an attempt to define an active stem cell population. We have used a recently developed dissociated cell reconstitution system, in which prostate epithelial stem and progenitor cells can be induced to form glandular tissue structures by embryonic urogenital sinus mesenchyme tissue when implanted under the kidney capsule, to study such stem cells.

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